Process for the preparation of sulfonylurea derivatives

Abstract: The present invention relates to a novel process for preparing sulfonylurea derivatives of formula (I) in a high purity and a high yield characterized in that a sulfonylchloride of formula (V) is reacted with 2-amino-4,6-dimethoxypyrimidine of formula (VII) in the presence of a metal cyanate and an organic base catalyst or a compound of formula (VIII) is reacted with 2-amino-4,6-dimethoxypyrimidine of formula (VII): wherein R¹ represents hydrogen, C₁-C₄ alkyl or phenyl, R² represents hydrogen, C₁-C₄ alkyl, allyl or propargyl and R³ represents hydrogen, methyl, ethyl or phenyl, and to a process for preparing the sulfonylchloride compound of formula (V) above and the compound of formula (VIII) above, both of which are useful as an intermediate compound for preparing the sulfonylurea derivative of formula (I) and to a novel intermediate compound of formula (VIII) as defined above.

Description: BACKGROUND OF THE INVENTION 1. Field of Invention The present invention relates to a novel process for preparation of sulfonylurea-based derivatives. Particularly, the present invention relates to a novel process for preparation of sulfonylurea derivatives having the following general formula (I), wherein R 1 represents hydrogen, C 1 -C 4 alkyl or phenyl; R 2 represents hydrogen, C 1 -C 4 alkyl, allyl or propargyl; and R 3 represents hydrogen, methyl, ethyl or phenyl. 2. Background Art The sulfonylurea derivative of formula (I) above is a known herbicide compound and processes for preparing the same are disclosed in numerous publications. For example, European Early Published Patent No. 87,780 discloses the three methods for preparing the compound (I), in which the first method comprises reacting an isocyanate of formula (II) with an amine compound of formula (VII); the second method comprises reacting an amine of formula (III) with an isocyanate of formula (VI); and the third method comprises reacting a carbamate of formula (IV) with an amine compound of formula (VII): wherein R 1 , R 2 and R 3 are as defined above. Both the first and second methods as described above are the general methods for preparing sulfonylurea derivatives by synthesizing and separating isocyanates which are then reacted with amines. However, the isocyanate used as the starting material in these methods is synthesized by reacting the amine derivative of formula (III) or (VII) with a poisonous substance, phosgene. Accordingly, such methods using the isocyanate have some disadvantages in that mass use of phosgene in the industrial scale requires a special safety equipment, hydrochloric acid produced as by-product should be treated and the remaining phosgene should be recovered. Further, when the compound of formula (I) is prepared by reacting such isocyanate compound with the amine derivative, the yield of the desired product (I) is as low as 70 to 80%. Moreover, as shown in the following reaction scheme, the first method produces the sulfonylurea derivative of formula (I) starting from the sulfonylchloride of formula (V) via the isocyanate of formula (II) according to a complicated multi-step procedure. Accordingly, this first method is disadvantageous in application to the mass production in the industrial scale. In addition, the third method as described above is a method identical to the method described in Japanese Laying-open Patent Publication No. (Hei) 03-200742 which requires a stringent reaction condition including high reaction temperature and produces the desired product (I) in a low yield. Therefore, this method is also unsuitable to the industrial scale production. Thus, the present inventors have extensively studied to find out a method which can conveniently prepare the desired compound of formula (I) in a simple manner. As a result we have identified a novel single-step method capable of preparing the desired compound (I) in a high purity and in a high yield. Therefore, it is an object of the present invention to provide a novel process for preparing the sulfonylurea derivative having the general formula (I) as defined above. The more pertinent and important features of the present invention have been outlined above in order that the detailed description of the invention which follows will be better understood and that the present contribution to the art can be fully appreciated. Those skilled in the art can appreciate that the conception and the specific embodiment disclosed herein may be readily utilized as a basis for modifying or designing other structures for carrying out the same purposes of the present invention. Further, those skilled in the art can realize that such equivalent constructions do not depart from the spirit and scope of the invention as set forth in the claims. DISCLOSURE OF INVENTION The present invention relates to a novel process for preparing the desired sulfonylurea derivative of formula (I). Specifically, the present invention is to provide a process for preparing the desired compound of formula (I) which comprises reacting sulfonylchloride of formula (V) with 2-amino-4,6-dimethoxypyrimidine (VII) in the presence of a metal cyanate and an organic base catalyst selected from the group consisting of trialkylamines, pyridine derivatives and cyclic tertiary amines as depicted in the following reaction scheme (A). In the above reaction scheme, R 1 , R 2 and R 3 are as defined above, and M represents a monovalent metal atom. The method (A) according to the present invention is carried out by reacting sulfonylchloride of formula (V) with 2-amino-4,6-dimethoxypyrimidine of formula (VII) in the presence of a metal cyanate and an organic base catalyst as defined above. Since the reaction of the method (A) according to the present invention is carried out in a stoichiometric manner, the starting material and the reactant can be reacted together in the equimolar amounts. However, considering the reaction efficiency, it is preferable that each of sulfonylchloride of formula (V) and the metal cyanate is used in the ratio of 1.0 to 2.0 equivalent weights with respect to the amine compound of formula (VII). Further, in view of the fact that the compound of formula (V) is relatively expensive it is preferable to use the compound of formula (V) in the ratio of 1.0 to 1.2 equivalent weights with respect to the amine compound (VII). Metal cyanate which can be used in this reaction includes a monovalent alkali metal cyanate, preferably sodium cyanate or potassium cyanate. The organic base which is used as a catalyst in the method (A) of the present invention is the most important factor which can determine the reaction rate and the reaction selectivity and includes tertiary alkylamine, pyridine derivative or cyclic tertiary amine. Particularly, when pyridine or triethylamine is used as the catalyst, the best result can be provided in view of the reaction selectivity and yield. The reaction result becomes better as the used amount of the organic base is increased in the range of 0.01 to 2.0 equivalent weight with respect to the amine of formula (VII). However, considering the economical view, it is preferable that the organic base is used in the ratio of 0.1 to 1.0 equivalent weight with respect to the amine compound of formula (VII). The solvent which can be used in this reaction (A) may be a single solvent selected from the group consisting of halogenated hydrocarbons and aromatic hydrocarbons such as dichloromethane, trichloromethane, 1,2-dichloroethane, etc., aprotic polar solvents such as dimethylformamide, dimethylsulfoxide, etc., ethers such as ethyl ether, tetrahydrofuran, dioxane, etc., nitriles such as acetonitrile, propionitrile, etc., ketones such as acetone, methylethyl ketone, diisopropyl ketone, etc., and the like, or a mixture of two or more solvents selected therefrom. In this case, the solvent is preferably used under anhydrous condition where it is possible. Although the reaction temperature can be varied within a relatively broad range, the reaction may preferably be carried out at 0°C to the refluxing temperature of the solvent used therein. When considering the reaction rate, the production of by-products and the like, it is particularly preferable that the reaction is carried out at 25 to 45°C. In this case, the reaction generally takes 0.5 to 4.0 hours. When sulfonylchloride of formula (V) is reacted with metal cyanate and the amine compound of formula (VII) according to the method (A) under such a special reaction condition, the desired sulfonylurea derivative of formula (I) can be obtained in a high yield of 88% or more and in a high purity without production of by-product. Sulfonylchloride of formula (V) which is used as the starting compound in the method (A) for preparing the sulfonylurea derivative of formula (I) according to the present invention is a compound known as an intermediate compound useful for preparation of the sulfonylurea-based herbicide. European Early Published Patent No. 87,780 as mentioned above also describes the method for preparing the intermediate compound of formula (V), in which a compound of formula (IX) is reacted with chlorine gas to prepare the pyrazole sulfonylchloride compound of formula (V), as depicted in the following reaction scheme: wherein R 1 , R 2 and R 3 are as defined above, and R 4 represents hydrogen or benzyl. However, since such known method uses chlorine gas which is highly poisonous to humans, the reaction should be practiced by means of a special safety apparatus. Further, this method has a disadvantage in that the by-product such as the compound of the following general formula (X): wherein R 1 , R 2 and R 3 are as defined above and X represents hydrogen or Cl, may be produced in a substantial amount due to the excessive strong reactivity of chlorine gas. The present invention establishes a method in which aqueous hydrochloric acid solution and hydrogen peroxide solution which are easy to handle and can be readily controlled in their reactivities are used in place of chlorine gas, and therefore the problems involved in the known method above can be solved. Specifically, according to the present invention the pyrazole sulfonylchloride derivative of formula (V) can be simply prepared by reacting a pyrazole disulfide derivative of formula (XI) with aqueous hydrochloric acid solution and hydrogen peroxide solution as depicted in the following reaction scheme: wherein R 1 , R 2 and R 3 are as defined above. The process for preparing the compound of formula (V) as defined above is a novel method which was never described in prior art up to the present. According to the process for preparing the compound of formula (V), the reaction can be carried out either by reacting together the starting compound and the reactant each of which is dissolved in a separate solvent or by dissolving the starting compounds directly in aqueous hydrochloric acid solution without any solvent. When the reaction is carried out using the solvent, the solvent which can preferably be used may be an organic solvent, for example, optionally halogenated alkane solvents such as n-hexane, dichloromethane, etc, toluene and the like. In this reaction, aqueous hydrochloric acid solution and hydrogen peroxide solution can be used in the ratio of 2.0 equivalent weights or more with respect to the starting disulfide compound of formula (XI) without any special limitation. However, in view of the fact that the production of by-products should be minimized, the reaction time should be shortened and the reaction efficiency should be increased, it is preferable that they are used in the ratio of 6.0 to 8.0 equivalent weights, respectively, with respect to the disulfide compound (XI). In addition, the reaction time of this reaction is prolonged in the case of the inner temperature of the reaction vessel below 20°C whereas the yield of the desired compound of formula (V) may be decreased at the temperature above 50°C due to hydrolysis of the compound of formula (V). Accordingly, the reactants should be carefully introduced so that the inner temperature of the reaction vessel can be maintained in the range of 30 to 50°C, more preferably 35 to 45°C. The disulfide compound of formula (XI) which can be used as the starting compound in the process for preparing the compound of formula (V) is a known compound and can be prepared, for example, by reacting a dithiocarbazate derivative of formula (XII) with a base and then oxidizing the reaction product in a conventional manner according to the method described in Korean Patent Application No. 92-24734 which belongs to the present inventors, as depicted in the following reaction scheme: wherein R 1 , R 2 and R 3 are as defined above, and R represents C 1 -C 4 alkyl, C 2 -C 4 alkenyl, aralkyl(preferably benzyl) or aryl(preferably phenyl). The sulfonylchloride compound of formula (V) can be prepared according to the following method as explained in the method for preparation of sulfonylchloride compound of formula (V) which is the starting compound in the method (A) above: wherein R 1 , R 2 and R 3 are as defined above. The present invention will be more specifically illustrated by the following examples. However, it should be understood that the present invention is not limited by these examples in any manner. Example 1 : Preparation of bis(4-ethoxycarbonyl-1-methylpyrazole)-5-disulfide 2.12g(10.0 mmole) of benzyl 2-methyldithiocarbazate and 2.25g(10.2 mmole) were mixed with 2.40g of anhydrous ethanol and the mixture was heated to dissolve all the substances. To this heated mixture was added 3.89g of 21% sodium ethoxide and the mixture was refluxed for 8 hours and then distilled in vacuo to remove the solvent. The residue was dissolved in 2.50g of dichloromethane and 3.00g of water. The aqueous layer was adjusted to pH 7 with 20% sulfuric acid and 0.48g of 35% aqueous hydrogen peroxide solution was added thereto over one hour at room temperature. The reaction mixture was continuously stirred for further one hour at room temperature and allowed to separate the layers. The separated organic layer was dried over anhydrous magnesium sulfate and distilled in vacuo to remove the solvent to obtain 1.70g of the title compound (Yield 92%, Purity 98%). Example 2 : Preparation of 4-ethoxycarbonyl-1-methylpyrazole-5-sulfonylchloride 1.67g(4.5 mmole) of the disulfide compound prepared in Example 1 was added to 3.75g(36.0 mmole) of 35% aqueous hydrochloric acid solution and 2.00g of dichloromethane at room temperature and the reaction mixture was warmed to 40°C and then maintained for 30 minutes at the same temperature. To this mixture was added 2.62g(27.0 mmole) of 35% aqueous hydrogen peroxide solution at 40 to 45°C over one hour and the whole mixture was continuously stirred for further one hour and then allowed to separate the layers. The separated organic layer was dried over anhydrous magnesium sulfate and the solvent was removed therefrom to obtain 2.16g of the title compound (Yield 95%, Purity 95%). Example 3 : Preparation of 4-ethoxycarbonyl-1-methyl-5-pyrazole disulfide 30.6g of methyl 3-[2',2'-(diethoxycarbonyl)ethylidene]-2-methyldithiocarbazate and 8g of sodium ethoxide were added to 250ml of absolute ethanol and the mixture was heated under reflux in the nitrogen atmosphere for about 10 hours. When the reaction was completed, ethanol was distilled off and 200ml of water and 500ml of methylene dichloride were added to the residue. The mixture was adjusted to approximately pH 8 with 98% sulfuric acid to separate the layers. The aqueous layer was collected and then adjusted to pH 2. The resulting product was extracted with 500ml of methylene dichloride. 5.0g of 38% hydrogen peroxide was added to the methylene dichloride layer and the mixture was stirred for 3 hours at room temperature to complete the reaction. The reaction mixture was allowed to separate the layers and the organic layer was collected, dried over anhydrous magnesium sulfate and then distilled in vacuo to remove the solvent to obtain 16.8g of the title compound as brown solid (Yield 91%, Purity 98%). Example 4 : Preparation of 4-ethoxycarbonyl-1-methylpyrazole-5-sulfonylchloride 370g of 4-ethoxycarbonyl-1-methyl-5-pyrazole disulfide, 390g of dichloromethane and 834g of 35% aqueous hydrochloric acid solution were introduced into a reaction flask. The reaction mixture was stirred at room temperature to dissolve the starting material and then 560g of 36% hydrogen peroxide was slowly added dropwise thereto over 2 hours during which the inner temperature of the flask should be maintained at approximately 40°C. After the addition of hydrogen peroxide was completed, the reaction mixture was stirred for further 30 minutes while maintaining the same temperature to complete the reaction, cooled to room temperature and then allowed to separate the layers. The separated organic layer was dried over anhydrous magnesium sulfate and the solvent was then removed therefrom to obtain 476g (Yield 94%) of the title compound as yellow liquid substance (Purity 94% as measured by gas chromatography). Example 5 : Preparation of 1-[[(4-ethoxycarbonyl-1-methylpyrazole-5-sulfonyl)amino]carbonyl]pyridinium hydroxide inner salt 1.08g(16.6 mmole) of anhydrous sodium cyanate, 1.25g(15.8 mmole) of dry pyridine and 20.0g of dry acetonitrile were mixed together and the resulting mixture was then stirred under nitrogen atmosphere while maintaining the temperature of 40°C. To this mixture was added 3.80g(15.0 mmole) of 4-ethoxycarbonyl-1-methylpyrazole-5-sulfonylchloride over one hour. The reaction mixture was then stirred for further 2 hours while maintaining the temperature of 40 to 45°C to complete the reaction. After the reaction was completed, the reaction solution was filtered under nitrogen atmosphere. The solvent and the remaining pyridine were removed from the filtrate at normal temperature by means of a vacuum pump to obtain the crude product which was then washed with 10.00g of dry ethyl ether and dried to obtain 4.68g (Yield 92%) of the title compound as the white solid. 1 H NMR (CDCl 3 ) : δ 9.38(2H), 8.30(1H), 7.85(1H), 7.82(2H), 4.34(3H, CH 3 -N ), 4.25(2H, OCH 2 -), 1.30(3H, C-CH 3 ) IR (cm -1 ) : 3120, 3075, 2986, Example 6 : Preparation of 1-[[(4-ethoxycarbonyl-1-methylpyrazole-5-sulfonyl)amino]carbonyl]pyridinium hydroxide inner salt 2.53g(10 mmole) of 4-ethoxycarbonyl-1-methylpyrazole-5-sulfonylchloride was dissolved in 10.00g of anhydrous acetonitrile. To the resulting solution was added dropwise 0.83g(10.5 mmole) of dry pyridine over 5 minutes under nitrogen atmosphere by means of a syringe and the mixture was maintained at 40°C. To this mixture was added 0.72g(11.0 mmole) of anhydrous sodium cyanate and the mixture was stirred while maintaining the temperature of 40 to 45°C to complete the reaction. Then, the reaction mixture was treated according to the same procedure as Example 5 to obtain 3.50g (Yield 90%) of the title compound as the white solid substance. 1 H NMR (CDCl 3 ) : δ 9.39(2H), 8.30(1H), 7.85(1H), 7.83(2H), 4.34(3H, CH 3 -N ), 4.25(2H, OCH 2 -), 1.30(3H, C-CH 3 ) IR (cm -1 ) : 3120, 3075, 2986, Example 7 : Preparation of N-[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]-4-ethoxycarbonyl-1-methylpyrazole-5-sulfonamide 7.27g of anhydrous sodium cyanate, 15.78g of 2-amino-4,6-dimethoxypyrimidine, 8.04g of pyridine and 40g of dry acetonitrile were mixed together and the mixture was warmed to 45°C under nitrogen atmosphere. To this mixture was added 28.46g of 1-methyl-4-ethoxycarbonylpyrazole-5-sulfonylchloride over 2 hours and the reaction mixture was stirred for further 2 hours while maintaining the temperature of 45°C. After the completion of the reaction was identified by liquid chromatography, the reaction product was extracted with 200g of dichloromethane and 40g of 5% aqueous sulfuric acid solution. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The organic solvent was removed from the product to obtain 41.30g (Yield 98%) of the title compound as a solid state. Example 8 : Preparation of N-[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]-4-ethoxycarbonyl-1-methylpyrazole-5-sulfonamide 2.603g of 4-ethoxycarbonyl-1-methylpyrazole-5-sulfonylchloride was dissolved in 20.0ml of acetonitrile. To the resulting solution were added 0.715g of sodium cyanate and 1.552g(10.0mM) of 4,6-dimethoxy-2-aminopyrimidine with stirring. The reaction mixture was maintained at 40°C for about 10 minutes and then 0.396g of pyridine was added dropwise thereto over 5 minutes via a syringe. While maintaining the temperature of 40 to 45°C, the reaction mixture was continuously and vigorously stirred for 3 hours to complete the reaction. After the reaction was completed, the reaction mixture was adjusted to pH 4 by adding 5% aqueous sulfuric acid solution and dichloromethane to extract the reaction product. The extracted organic layer was dried over anhydrous magnesium sulfate and then filtered. The organic solvent was removed from the filtrate to obtain 4.103g (Yield 99%) of the title compound in the solid state. Examples 9 to 15 According to the same procedure as Example 7, 2.603g of 4-ethoxycarbonyl-1-methylpyrazole-5-sulfonylchloride was reacted with 1.552g(10.0mM) of 2-amino-4,6-dimethoxypyrimidine under the reaction conditions as shown in the following table to obtain the same desired compound as in Example 7. The results obtained in these examples are described in the following table. Example No. Metal cyanate (Equi.) Catalyst (Equi.) Solvent (20.0ml) Reaction Temp.(°C) Reaction Time(hr) Yield 9 NaOCN (1:1) pyridine(0.5) CH 3 CN 25 12 95 10 NaOCN (1:1) pyridine(0.5) CH 3 CN reflux 0.5 97 11 NaOCN (1:1) pyridine(0.5) CH 2 Cl 2 reflux 5 90 12 KOCN (1:1) pyridine(0.5) CH 3 CN 40 2 98 13 KOCN (1:1) pyridine(0.5) CH 2 Cl 2 reflux 5 88 14 NaOCN Not used CH 3 CN 25 12 42 15 NaOCN TBAB (0.1) CH 3 CN 25 12 50 Example 16 : Preparation of N-[(4-methoxy-6-methylpyrimidin-2-yl)aminocarbonyl]-1-methylpyrazole-5-sulfonamide 23.8g of 4-methoxycarbonyl-1-methylpyrazole-5-sulfonamide was dissolved in 100g of acetonitrile and 8.0g of sodium cyanate and 13.9g of 2-amino-4-methoxy-6-methylpyrimidine were added thereto with stirring. The reaction mixture was maintained at 40°C for about 10 minutes. To this mixture was added dropwise 0.3g of pyridine over 5 minutes. The whole mixture was vigorously and continuously stirred for 2 hours while maintaining the temperature of 40 to 45°C to complete the reaction. The mixture was then treated according to the same procedure as Example 7 to obtain 35.3g (Yield 92%) of the title compound. Example 17 : Preparation of N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)aminocarbonyl]-1,3-dimethyl-5-methoxycarbonylpyrazole-4-sulfonamide 25.2g of 1,3-dimethyl-5-methoxycarbonylpyrazole-4-sulfonylchloride, 13.9g of 2-amino-4-methoxy-6-methyl-1,3,5-triazine, 9.7g of potassium cyanate and 0.3g of pyridine were dissolved in 100ml of acetonitrile and the mixture was allowed to react for 2 hours at 50°C. The reaction mixture was then treated according to the same procedure as Example 7 to obtain 35.5g (Yield 89%) of the title compound. Example 18 : Preparation of N-[(4,6-dimethoxypyrimidin-2-yl)aminocarbonyl]-4-ethoxycarbonyl-1-methylpyrazole-5-sulfonamide 3.42g(10.1 mmole) of 1-[[(4-ethoxycarbonyl-1-methylpyrazole-5-sulfonyl)amino]carbonyl]pyridinium hydroxide was dissolved in 10.00g of dry acetonitrile. To the resulting solution was added 1.55g(10.0 mmole) of 2-amino-4,6-dimethoxypyrimidine with stirring. The reaction mixture was stirred for one hour while maintaining the temperature of 40 to 45°C to complete the reaction. After the reaction was completed, 25.00g of water was added to the reaction solution. The mixture was then adjusted to pH 5 to 6, cooled to 25°C and filtered. The resulting product was washed with water and acetonitrile and then dried to obtain 4.10g (Yield 99%) of the title compound as the white powder. The more pertinent important features of the present invention have been outlined above in order that the detailed description of the invention will be better understood and that the present contribution to the art can be fully appreciated. Those skilled in the art can appreciate that the conception and the specific embodiment disclosed herein may be readily utilized as a basis for modifying or designing other structures for carrying out the same purposes of the present invention. Further, those skilled in the art can realize that such equivalent constructions do not depart from the spirit and scope of the invention as set forth in the claims.

Claims: A process for preparing sulfonylurea derivatives having the following general formula (I), wherein R 1 represents hydrogen, C 1 -C 4 alkyl or phenyl; R 2 represents hydrogen, C 1 -C 4 alkyl, allyl or propargyl; and R 3 represents hydrogen, methyl, ethyl or phenyl, characterized in that a sulfonylchloride of formula (V), wherein R 1 , R 2 and R 3 are as defined above, is reacted with 2-amino-4,6-dimethoxypyrimidine of formula (VII), in the presence of a metal cyanate and an organic base catalyst selected from the group consisting of trialkylamines, pyridine derivatives and cyclic tertiary amines. The process according to claim 1, characterized in that said metal cyanate is sodium cyanate or potassium cyanate. The process according to claim 1, characterized in that the organic base catalyst is pyridine. The process according to claim 1 or 3, characterized in that the organic base catalyst is used in an amount of 0.1 to 1.0 equivalent weight with respect to 2-amino-4,6-dimethoxypyrimidine of formula (VII). The process according to claim 1, characterized in that the reaction is carried out in the presence of a solvent. The process according to claim 5, characterized in that the solvent is a single solvent selected from the group consisting of dichloromethane, trichloroethane, 1,2-dichloroethane, benzene, toluene, chlorobenzene, dichlorobenzene, dimethylformamide, dimethylsulfoxide, ethyl ether, tetrahydrofuran, dioxane, acetonitrile, acetone and diisopropyl ketone, or a mixture of two or more solvents selected therefrom. The process according to claim 6, characterized in that the solvent is acetonitrile or dichloromethane. The process according to claim 1, characterized in that the reaction temperature is 25 to 45°C.

Inventors: CHOI JONG KWON, CHUNG IN BAE, HEO TAE HO, LEE JAE CHOL, SA JON SIN, SUH BYOUNG WOO, CHOI, JONG KWON, CHUNG, IN BAE, HEO, TAE HO, LEE, JAE CHOL, SA, JON SIN, SUH, BYOUNG WOO, Chung, In Bae Lucky Apt. B-103, Heo, Tae Ho Lucky Apt. A-204
Applicants: LUCKY LTD, LUCKY LTD.
Application year: 1994
Main classification: C07D403
IPC codes: C07D401, C07D521, C07D403, C07B61, A01N43, B01J31, C07D231